Aldose reductase may participate in the development of diabetes complications. Aldose reductase is the initial enzyme in the intracellular polyol pathway. This pathway involves the conversion of glucose into glucose alcohol (sorbitol). High glucose levels increase the flux of sugar molecules through the polyol pathway, which causes sorbitol accumulation in cells. Osmotic stress from sorbitol accumulation has been postulated as an underlying mechanism in the development of diabetic microvascular complications, including diabetic retinopathy. In animal models, sugar alcohol accumulation has been linked to microaneurysm formation, thickening of basement membranes, and loss of pericytes. Treatment studies with aldose reductase inhibitors, however, have been disappointing